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Emerging evidence suggests that long non-coding RNAs (lncRNAs) are significant regulators in the pathological process of ischemic stroke (IS). However, little is known about lncRNAs and their roles in IS. In this study, we aimed to screen out differentially expressed lncRNAs and revealed the underlying mechanisms in IS. The results of bioinformatic analysis showed that lncRNA MEG3 and Sema3A were overexpressed in IS samples, while miR-424-5p was lower-expressed. Correlation between MEG3/miR-424-5p, and miR-424-5p/Sema3A were predicted with miRanda and TargetScan, and verified by dual luciferase assay. Inhibition of MEG3 remarkably increased the expression of miR-424-5p and decreased the expression of Sema3A, which also led to in an increased cell viability and decreased cellular apoptosis in oxygenglucose deprivation and reoxygenation (OGD/R) model, as well as an activated MAPK signaling pathways. Consistently, MEG3 was upregulated in MCAO mice, knockdown of MEG3 reduced the infarct volume and improved neurobehavioral outcomes in rats following MCAO. In conclusion, it was demonstrated that MEG3 accelerated the process of IS by suppressing miR-424-5p, which targeted Sema3A and the activated MAPK pathway. These results might provide useful information for exploring the potential therapeutic targets in IS.

Puerarin (PUE) is a good candidate for treating stroke, but its low concentration in brain after administration limits its curative efficacy. The aim of the present work was to design and characterize PUE loaded poly(butylcyanoacrylate) nanoparticles (PBCN) coated with polysorbate 80 (Ps 80), and to evaluate the effect of PBCN on the permeability of PUE across the blood-brain barrier (BBB) and the effect of PUE loaded PBCN on the cerebral ischemia/reperfusion injury. PUE loaded PBCN were successfully prepared by anionic polymerization method with the mean particle size of 201.2 nm and the zeta potential of −7.72 mV. The in vitro release behavior of PUE from the nanoparticles showed a biphasic profile manner with an initial burst release followed by a sustained release. The results of pharmacokinetic and biodistribution to brain performed in mice after intravenous administration showed that the drug concentrations in blood and brain for PUE loaded PBCN were both greater than these for the free drug. Moreover, compared with free drug, the vein injection of PUE loaded PBCN exerted the better neuroprotective effect in rats with focal cerebral ischemic injury via significantly decreasing neurological deficit scores, increasing body weight, lowing brain water content, and reducing the infarct volume. The results indicated that this preparation may reduce the total dose required for the stroke therapy with concurrent reduction in dose related toxicity. All these findings suggest that PBCN could enhance the transport of PUE to brain and have a potential as a neuroprotective agent in the focal cerebral ischemic injury.